The objective is to define pathogenic mechanisms involved in chronic fatigue syndrome. Studies will concentrate on patients with chronic fatigue + cognitive impairment following infection by the spirochete B.burgdorferi (Bb) (the cause of Lyme disease). Controls will be matched Bb-infected subjects without such problems. Subjects will be evaluated at single time points and serially for clinical parameters (using fatigue and cognition rating scales) and immune parameters. The following specific points will be addressed: 1. Are predisposing factors involved? Document HLA-DR type, allergy history, depression/psychologic profile, and skin test response of patients vs. controls. 2. Is immune activation involved? Examine blood and cerebrospinal fluid for immune complexes (IC) using polyethylene glycol, chromatography, and Raji cell assay; spontaneous, mitogen, and antigen-induced lymphocyte proliferation; and cytokines/soluble markers using ELISA in patients vs. controls. 3. Is immune activation directed against Bb? Isolate IC to probe for anti-Bb antibodies. Compare in vitro lymphocyte reactivity and cytokine production to Bb in patients vs. controls. 4. Compare the immune profile of patient with fatigue alone vs cognitive impairment. Correlate humoral, cellular, and soluble immune parameters with measured clinical parameters of fatigue and cognition. 5. Do fatigue or cognitively impaired patients have persistent Bb infection? Probe isolated IC for Bb antigens using monoclonal/polyclonal antibodies, ELISA, and immunoblot. This study targets a specific subgroup of postinfectious fatigue patients to examine the role of immune activation and persistent infection in their fatigue, and the relationship of cognitive impairment to fatigue. This work should provide insights for the heterogeneous group of patients with chronic fatigue syndromes.